Women Underrepresented in Clinical Trials for High-Risk Medical Implants

Women are more than 50% of the global population, yet they are underrepresented in studies for high-risk medical implants for commonly performed cardiovascular, orthopedic, and other surgeries, according to a systematic review published June 10 in JAMA Internal Medicine.

Researchers in Israel analyzed women’s representation in high-risk medical implant trials published January 2016 to May 2022, considering such things as participation-to-prevalence ratio (PPR).

They found that women are participating in device trials but not at the rate they need to be. The researchers reviewed 195 trials, 67% of which were cardiovascular studies for such devices as stents, valves, and pacemakers, and 20% for orthopedic prostheses. The researchers found the number of women randomized in the trials reporting gender was a median 33%, ranging between 7% to 100%.

Cardiovascular device trials had a mean 29% of women represented. Women were better represented in orthopedic trials, at a mean 46%.

“The PPR for most common devices was less than 0.8, implying underrepresentation of women, as has been demonstrated in older device trials showing lower representation than drug or lifestyle interventions,” according to the paper. 

History: No studies for you!

Historically, women have been excluded from medical studies, and the findings of those studies in men were generalized to women. People’s reasoning for excluding women ranged from fertility or pregnancy concerns to the “the perception of the male as representative of the human species and, therefore, the norm,” according to a literature review published in 2022 in Women's Health Reports.

In recent decades, government funding agencies, researchers, and others realized women are suffering health-wise because of the lack of gender-specific data, and they need to be adequately represented in research for drugs and devices. Concerning the latter, the FDA’s Center for Devices and Radiologic Health, for example, launched the Health of Women Program to protect and promote women’s health related to the performance of medical devices in women. The National Institutes of Health (NIH) is required by law to ensure that women and minorities are included in “clinical research as appropriate to the scientific question under study,” according to NIH.gov, which has an inclusion and outreach toolkit for engaging, recruiting, and retaining women in clinical trials.

Body size, hormones, comorbidities and parity (oh my!)

Body size and hormonal variations are among the sex-related covariates that can impact performance data on devices in women, according to the review authors.

“Women are not little men,” said Marissa Fayer, chief executive officer of HERhealthEQ, a global nonprofit focused on women’s health in developing countries. “We’re different sizes. We have different conditions. And we have a different anatomy.”

Sizing down on device use for women based on research predominately in men isn’t a good plan for women’s health, according to Fayer.

The potential implications of not adequately studying device safety and efficacy in women is particularly concerning given that heart disease, for example, is the number one killer of women. And women are more likely than men to have osteoarthritis of the hip and knee — for which total hip or knee arthroplasty is the recognized surgical treatment, according to a paper published this year in the Journal of Arthroplasty.  

Overcoming recruitment obstacles

Fayer said she doesn’t think device manufacturers and device researchers are making a concerted effort to exclude women.

“I just don’t think there’s a concerted effort to include them,” she told MD+DI. “You have to make an active and concerted effort to go forward and find people that are more diverse.”

JAMA review authors report that “obstacles to women’s inclusion include concerns about fetal consequences, underdiagnosis or under-referral of women, perceived recruitment challenges, and inclusion and exclusion criteria favoring men.”

Potential solutions for more gender balanced recruiting, including improving physician awareness of the need to recruit more women — because the screening stage is the most limiting step for women’s recruitment, and to include women researchers as trial leaders, as women-led studies are more likely to include women.

Women should not only be leading trials, but also helping to design medical devices, according to Fayer, an engineer who has worked in med-tech for 24 years.

In their article Addressing Demographic Disparities in Clinical Trials, Harvard Business Review authors suggested three things for creating representative patient data: Know what representative means for a device’s use and set goals for recruiting based on that; rather than recruiting from scratch, consider using disease registries (which might be more inclusive); and recruit beyond the confines of a traditional academic medical center.

Along the lines of going outside academic centers to recruit women, Fayer added that researchers should go to where their potential participants are in the community, which could include women’s health centers, churches, beauty shops, etc.

And make it easier for women to participate. If they’re working two jobs and have children at home, consider helping them to make their study appointments with Uber rides, childcare, or by paying for missed work.

Fayer stressed the need for a conscious concerted effort aimed at including women.

“Not just ‘[groan], we have to include women.’ More of a, ‘We have to include women to make sure our product is equitable in serving the entire population,’” she said.